The project is extending earlier observations we have made concerning a pronounced potentiation of the lethality of morphine when rats were pretreated with a catechol-O-methyltransferase inhibitor, tropolone. It will evaluate combinations of other narcotic analgesics and other COMT inhibitors for similar potentiation of toxicity. CNS monoamines will be investigated for their relationship to the observed toxic phenomena. Possible antidotal measures will be evaluated in the light of the possible clinical occurrence of a similar toxicology for COMT inhibitors which have been considered for clinical application.